Substituted-4-quinolones

Abstract

Substituted-4-quinolones of the formula (I): wherein R 1 is a straight or branched chain, saturated or ethylenically-unsaturated aliphatic hydrocarbyl group containing 1 to 18 carbon atoms which may optionally be substituted by one or more substituent groups selected from halo, 1-6C alkoxy, carboxy, 1-6C alkoxycarbonyl and NR 6 R 7 , wherein each of R 6 and R 7 is independently selected from H and 1-6C alkyl or R 6 and R 7 together with the N atom to which they are attached form a saturated heterocyclic group selected from piperidino, piperazino and morpholino; R 2 is a group selected from H, —OH, halo, —CHO, —CO 2 H and CONHR 8 wherein R 8 is H or a 1-6C alkyl; each of R 3 , R 4 and R 5 is independently selected form H, —CH 3 , —OCH 3 and halo; or a non-toxic pharmaceutically-acceptable salt thereof, have use in the manufacture of a medicament for the treatment of a disease of a living animal body, including a human, which disease is responsive to the activity of an immunosuppressant. The preferred compound of the formula 1 is 2-n-heptyl-3-hydroxy-4(1H)-quinolone.

1. A method of suppressing T-cell proliferation in a living animal body by
 administering to the living animal body a therapeutically-effective amount of a compound of the formula I 
 
       
         
           
           
               
               
           
         
         wherein R1 is a straight or branched chain, saturated or ethylenically-unsaturated aliphatic hydrocarbyl group containing from 1 to 18 carbon atoms which may optionally be substituted by one or more substituent groups selected from halo, 1-6C alkoxy, carboxy, 1-6C alkoxycarbonyl and NR 6 R 7 , wherein each of R 6  and R 7  is independently selected from H and 1-6C alkyl or R 6  and R 7  together with the N atom to which they are attached form a saturated heterocyclic group selected from piperidino, piperazino and morpholin; R 2  is group selected from H, —OH, halo, —CHO, —CO 2 H and CONHR 8  wherein R 8  is H or a 1-6C alkyl; each of R 3 , R 4  and R 5  is independently selected from H, —CH 3 , —OCH 3  and halo; or a non-toxic pharmaceutically-acceptable salt thereof; 
         wherein said suppression of T-cell proliferation treats autoimmune diseases. 
       
     
     
       2. The method according to  claim 1 , wherein the compound has the formula I in which R 1  is a straight chain alkyl group having from 3 to 13 carbon atoms. 
     
     
       3. The method according to  claim 2 , wherein R 1  is n-heptyl. 
     
     
       4. The method according to  claim 1 , wherein R 2  is OH. 
     
     
       5. The method according to  claim 4 , wherein the compound of the formula I is 2-n-heptyl-3-hydroxy-4 (1 H)-quinolone. 
     
     
       6. The method according to  claim 1 , wherein the autoimmune disease is selected from the group consisting of psoriasis, multiple sclerosis and rheumatoid arthritis. 
     
     
       7. A method of treating an individual with psoriasis, said method comprising:
 applying topically to the individual a therapeutically-effective amount of an active compound to suppress T-cell proliferation at the site of topical application. wherein the active compound is formulated in a medicament for topical application and has the formula I 
 
       
         
           
           
               
               
           
         
         wherein R 1  is a straight or branched chain, saturated or ethylenically-unsaturated aliphatic hydrocarbyl group containing from 1 to 18 carbon atoms which may optionally be substituted by one or more substituent groups selected from halo, 1-6C alkoxy, carboxy, 1-6C alkoxycarbonyl and NR 6 R 7 , wherein each of R 6  and R 7  is independently selected from H and 1-6C alkyl or R 6  and R 7  together with the N atom to which they are attached form a saturated heterocyclic group selected from piperidino, piperazino and morpholino; R 2  is group selected from H, —OH, halo, —CHO, —CO 2 H and CONHR 8  wherein R 8  is H or a 1-6C akyl; each of R 3 , R 4  and R 5  is independently selected from H, —CH 3 , —OCH 3  and halo; or a non-toxic pharmaceutically-acceptable salt thereof. 
       
     
     
       8. The method of  claim 1 , wherein the medicament is an ointment, cream or lotion. 
     
     
       9. The method of  claim 7 , wherein the active compound is 2-n-heptyl-3-hydroxy-4(1H)-quinolone.